Molecular remission at the end of treatment is a necessary goal for a good outcome in ELN favorable-risk acute myeloid leukemia

a real-life analysis on 201 patients by the Rete Ematologica Lombarda network

Patrizia Zappasodi, Laura Marbello, Erika Borlenghi, Monica Fumagalli, Massimo Bernardi, Nicola Fracchiolla, Valentina Mancini, Matteo da Vià, Emanuele Ravano, Elisa Cerqui, Virginia Valeria Ferretti, Barbara Rocca, Celeste Calvello, Mario Cazzola, Carlo Castagnola, Giuseppe Rossi

Research output: Contribution to journalArticle

Abstract

Favorable acute myeloid leukemia (AML) patients (pts.) demonstrate a relatively good outcome with standard induction; thus, pts. are generally not addressed to allogeneic transplant in first remission. However, it is not clear if also in a real-life setting, the outcome is homogeneous in the different favorable molecular groups and which are the parameters significantly associated to an increased relapse risk, useful to suggest the need of an intensified approach. In order to clarify this point, we collected clinical data on consecutive unselected AML pts. assigned to favorable category (modified ELN 2010 due to the inclusion of double-mutated CEBPA-positive cases), diagnosed and treated in six centers of the Italian network Rete Ematologica Lombarda (REL) from 2007 to 2015. We assessed response (CR, mCR), relapse rate (CIR), and outcome (OS, DFS) after first-line treatment. A total of 201 pts. was studied and the analysis was performed globally and in each molecular group: t(8;21)(q22;q22)/RUNX1-RUNX1T1 (30 pts., 14.9%), inv. (16)(p13q22) or t(16;16)(p13q22)/CBFB-MIH11 (35 pts., 17.4%), normal karyotype and mutated NPM1 and negative FLT3-ITD (116 pts., 57.7%) or double-mutated CEBPA (CEBPAdm) (20 pts., 10%). Complete remission (CR) was obtained in 188 pts. (93.5%), molecular CR (mCR) in 114 (67.5%); After a median follow-up of 2.4 years, cumulative incidence of relapse (CIR) was documented in 78 of 188 responding pts. (41%) after a median time of 11.3 months. CIR was higher in the CBFB-MIH11 group, in pts. achieving only a hematological response without mCR (72.1 vs 28.1%, p < 0.001), in older pts. and it resulted independently associated with a lower median cytarabine cumulative dose (CCD). Median OS was not reached: after 5 years it was 66.3%, and median DFS was 5.3 years, both without difference among groups. Molecular CR reached at any time, during or after the end of first-line treatment, was significantly associated with better DFS, and in particular, mCR assessed at the end of treatment was confirmed in multivariate analysis as an independent prognostic factor both for DFS and OS. In conclusion, the present study confirms in a real-life context the overall good prognosis of favorable-risk AML; the achievement of any molecular negativity during first-line treatment, particularly when assessed at the end of treatment, is associated with lower relapse and better survival. Increasing age at diagnosis has a negative prognostic impact, while CCD higher than 18 g/sqm is associated with better outcome.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalAnnals of Hematology
DOIs
Publication statusAccepted/In press - Jul 15 2018

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Acute Myeloid Leukemia
Recurrence
Cytarabine
Therapeutics
Incidence
Karyotype
Multivariate Analysis
Transplants
Survival

Keywords

  • Acute myeloid leukemia
  • Favorable risk
  • Outcome
  • Real life

ASJC Scopus subject areas

  • Hematology

Cite this

@article{4af74aa0552d48aa810a8980bd4b3296,
title = "Molecular remission at the end of treatment is a necessary goal for a good outcome in ELN favorable-risk acute myeloid leukemia: a real-life analysis on 201 patients by the Rete Ematologica Lombarda network",
abstract = "Favorable acute myeloid leukemia (AML) patients (pts.) demonstrate a relatively good outcome with standard induction; thus, pts. are generally not addressed to allogeneic transplant in first remission. However, it is not clear if also in a real-life setting, the outcome is homogeneous in the different favorable molecular groups and which are the parameters significantly associated to an increased relapse risk, useful to suggest the need of an intensified approach. In order to clarify this point, we collected clinical data on consecutive unselected AML pts. assigned to favorable category (modified ELN 2010 due to the inclusion of double-mutated CEBPA-positive cases), diagnosed and treated in six centers of the Italian network Rete Ematologica Lombarda (REL) from 2007 to 2015. We assessed response (CR, mCR), relapse rate (CIR), and outcome (OS, DFS) after first-line treatment. A total of 201 pts. was studied and the analysis was performed globally and in each molecular group: t(8;21)(q22;q22)/RUNX1-RUNX1T1 (30 pts., 14.9{\%}), inv. (16)(p13q22) or t(16;16)(p13q22)/CBFB-MIH11 (35 pts., 17.4{\%}), normal karyotype and mutated NPM1 and negative FLT3-ITD (116 pts., 57.7{\%}) or double-mutated CEBPA (CEBPAdm) (20 pts., 10{\%}). Complete remission (CR) was obtained in 188 pts. (93.5{\%}), molecular CR (mCR) in 114 (67.5{\%}); After a median follow-up of 2.4 years, cumulative incidence of relapse (CIR) was documented in 78 of 188 responding pts. (41{\%}) after a median time of 11.3 months. CIR was higher in the CBFB-MIH11 group, in pts. achieving only a hematological response without mCR (72.1 vs 28.1{\%}, p < 0.001), in older pts. and it resulted independently associated with a lower median cytarabine cumulative dose (CCD). Median OS was not reached: after 5 years it was 66.3{\%}, and median DFS was 5.3 years, both without difference among groups. Molecular CR reached at any time, during or after the end of first-line treatment, was significantly associated with better DFS, and in particular, mCR assessed at the end of treatment was confirmed in multivariate analysis as an independent prognostic factor both for DFS and OS. In conclusion, the present study confirms in a real-life context the overall good prognosis of favorable-risk AML; the achievement of any molecular negativity during first-line treatment, particularly when assessed at the end of treatment, is associated with lower relapse and better survival. Increasing age at diagnosis has a negative prognostic impact, while CCD higher than 18 g/sqm is associated with better outcome.",
keywords = "Acute myeloid leukemia, Favorable risk, Outcome, Real life",
author = "Patrizia Zappasodi and Laura Marbello and Erika Borlenghi and Monica Fumagalli and Massimo Bernardi and Nicola Fracchiolla and Valentina Mancini and {da Vi{\`a}}, Matteo and Emanuele Ravano and Elisa Cerqui and Ferretti, {Virginia Valeria} and Barbara Rocca and Celeste Calvello and Mario Cazzola and Carlo Castagnola and Giuseppe Rossi",
year = "2018",
month = "7",
day = "15",
doi = "10.1007/s00277-018-3424-4",
language = "English",
pages = "1--9",
journal = "Annals of Hematology",
issn = "0939-5555",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - Molecular remission at the end of treatment is a necessary goal for a good outcome in ELN favorable-risk acute myeloid leukemia

T2 - a real-life analysis on 201 patients by the Rete Ematologica Lombarda network

AU - Zappasodi, Patrizia

AU - Marbello, Laura

AU - Borlenghi, Erika

AU - Fumagalli, Monica

AU - Bernardi, Massimo

AU - Fracchiolla, Nicola

AU - Mancini, Valentina

AU - da Vià, Matteo

AU - Ravano, Emanuele

AU - Cerqui, Elisa

AU - Ferretti, Virginia Valeria

AU - Rocca, Barbara

AU - Calvello, Celeste

AU - Cazzola, Mario

AU - Castagnola, Carlo

AU - Rossi, Giuseppe

PY - 2018/7/15

Y1 - 2018/7/15

N2 - Favorable acute myeloid leukemia (AML) patients (pts.) demonstrate a relatively good outcome with standard induction; thus, pts. are generally not addressed to allogeneic transplant in first remission. However, it is not clear if also in a real-life setting, the outcome is homogeneous in the different favorable molecular groups and which are the parameters significantly associated to an increased relapse risk, useful to suggest the need of an intensified approach. In order to clarify this point, we collected clinical data on consecutive unselected AML pts. assigned to favorable category (modified ELN 2010 due to the inclusion of double-mutated CEBPA-positive cases), diagnosed and treated in six centers of the Italian network Rete Ematologica Lombarda (REL) from 2007 to 2015. We assessed response (CR, mCR), relapse rate (CIR), and outcome (OS, DFS) after first-line treatment. A total of 201 pts. was studied and the analysis was performed globally and in each molecular group: t(8;21)(q22;q22)/RUNX1-RUNX1T1 (30 pts., 14.9%), inv. (16)(p13q22) or t(16;16)(p13q22)/CBFB-MIH11 (35 pts., 17.4%), normal karyotype and mutated NPM1 and negative FLT3-ITD (116 pts., 57.7%) or double-mutated CEBPA (CEBPAdm) (20 pts., 10%). Complete remission (CR) was obtained in 188 pts. (93.5%), molecular CR (mCR) in 114 (67.5%); After a median follow-up of 2.4 years, cumulative incidence of relapse (CIR) was documented in 78 of 188 responding pts. (41%) after a median time of 11.3 months. CIR was higher in the CBFB-MIH11 group, in pts. achieving only a hematological response without mCR (72.1 vs 28.1%, p < 0.001), in older pts. and it resulted independently associated with a lower median cytarabine cumulative dose (CCD). Median OS was not reached: after 5 years it was 66.3%, and median DFS was 5.3 years, both without difference among groups. Molecular CR reached at any time, during or after the end of first-line treatment, was significantly associated with better DFS, and in particular, mCR assessed at the end of treatment was confirmed in multivariate analysis as an independent prognostic factor both for DFS and OS. In conclusion, the present study confirms in a real-life context the overall good prognosis of favorable-risk AML; the achievement of any molecular negativity during first-line treatment, particularly when assessed at the end of treatment, is associated with lower relapse and better survival. Increasing age at diagnosis has a negative prognostic impact, while CCD higher than 18 g/sqm is associated with better outcome.

AB - Favorable acute myeloid leukemia (AML) patients (pts.) demonstrate a relatively good outcome with standard induction; thus, pts. are generally not addressed to allogeneic transplant in first remission. However, it is not clear if also in a real-life setting, the outcome is homogeneous in the different favorable molecular groups and which are the parameters significantly associated to an increased relapse risk, useful to suggest the need of an intensified approach. In order to clarify this point, we collected clinical data on consecutive unselected AML pts. assigned to favorable category (modified ELN 2010 due to the inclusion of double-mutated CEBPA-positive cases), diagnosed and treated in six centers of the Italian network Rete Ematologica Lombarda (REL) from 2007 to 2015. We assessed response (CR, mCR), relapse rate (CIR), and outcome (OS, DFS) after first-line treatment. A total of 201 pts. was studied and the analysis was performed globally and in each molecular group: t(8;21)(q22;q22)/RUNX1-RUNX1T1 (30 pts., 14.9%), inv. (16)(p13q22) or t(16;16)(p13q22)/CBFB-MIH11 (35 pts., 17.4%), normal karyotype and mutated NPM1 and negative FLT3-ITD (116 pts., 57.7%) or double-mutated CEBPA (CEBPAdm) (20 pts., 10%). Complete remission (CR) was obtained in 188 pts. (93.5%), molecular CR (mCR) in 114 (67.5%); After a median follow-up of 2.4 years, cumulative incidence of relapse (CIR) was documented in 78 of 188 responding pts. (41%) after a median time of 11.3 months. CIR was higher in the CBFB-MIH11 group, in pts. achieving only a hematological response without mCR (72.1 vs 28.1%, p < 0.001), in older pts. and it resulted independently associated with a lower median cytarabine cumulative dose (CCD). Median OS was not reached: after 5 years it was 66.3%, and median DFS was 5.3 years, both without difference among groups. Molecular CR reached at any time, during or after the end of first-line treatment, was significantly associated with better DFS, and in particular, mCR assessed at the end of treatment was confirmed in multivariate analysis as an independent prognostic factor both for DFS and OS. In conclusion, the present study confirms in a real-life context the overall good prognosis of favorable-risk AML; the achievement of any molecular negativity during first-line treatment, particularly when assessed at the end of treatment, is associated with lower relapse and better survival. Increasing age at diagnosis has a negative prognostic impact, while CCD higher than 18 g/sqm is associated with better outcome.

KW - Acute myeloid leukemia

KW - Favorable risk

KW - Outcome

KW - Real life

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U2 - 10.1007/s00277-018-3424-4

DO - 10.1007/s00277-018-3424-4

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